Background: Early in the SARS-CoV-2 pandemic, commentators warned that some COVID trials were inadequately conceived, designed and reported. Here, we retrospectively assess the prevalence of informative COVID trials launched in the first 6 months of the pandemic.Methods: Based on prespecified eligibility criteria, we created a cohort of Phase 1/2, Phase 2, Phase 2/3 and Phase 3 SARS-CoV-2 treatment and prevention efficacy trials that were initiated from 2020-01-01 to 2020-06-30 using ClinicalTrials.gov registration records. We excluded trials evaluating behavioural interventions and natural products, which are not regulated by the U.S. Food and Drug Administration (FDA). We evaluated trials on 3 criteria of informativeness: potential redundancy (comparing trial phase, type, patient-participant characteristics, treatment regimen, comparator arms and primary outcome), trials design (according to the recommendations set-out in the May 2020 FDA guidance document on SARS-CoV-2 treatment and prevention trials) and feasibility of patient-participant recruitment (based on timeliness and success of recruitment).Results: We included all 500 eligible trials in our cohort, 58% of which were Phase 2 and 84.8% were directed towards the treatment of SARS-CoV-2. Close to one third of trials met all three criteria and were deemed informative (29.9% (95% Confidence Interval 23.7–36.9)). The proportion of potentially redundant trials in our cohort was 4.1%. Over half of the trials in our cohort (56.2%) did not meet our criteria for high quality trial design. The proportion of trials with infeasible patient-participant recruitment was 22.6%.Conclusions: Less than one third of COVID-19 trials registered on ClinicalTrials.gov during the first six months met all three criteria for informativeness. Shortcomings in trial design, recruitment feasibility and redundancy reflect longstanding weaknesses in the clinical research enterprise that were likely amplified by the exceptional circumstances of a pandemic.

To provide a systematic overview of bioethical debate on somatic gene therapy as documented in the scientific literature. We performed a systematic review of reasons, following Strech and Sofaer approach, which is a method to systematically identify and classify arguments (reasons) used in the scientific literature. We identified 217 eligible publications retrieved from PubMed, Lilacs, PhilPapers, and Google Scholar. A meta-synthesis was performed to analyze the data. We extracted 189 arguments. Arguments were grouped into 23 categories. Twelve categories were classified as research-related, including the risk/benefit ratio, priorities and limits, informed consent, review, and monitoring. Eleven were classified as society-related, including population impact, human identity, public perception, human health. Our study provides a database of existing challenges and arguments of somatic gene therapy and may serve as the basis of normative analysis. By presenting collected arguments, we contribute to the discussion about the ethics and social dimensions of somatic gene therapy.

Drug repurposing is a strategy of identifying new potential uses for already existing drugs. Many researchers adopted this method to identify treatment or prevention during the COVID-19 pandemic. However, despite the considerable number of repurposed drugs that were evaluated, only some of them were labeled for new indications. In this article, we present the case of amantadine, a drug commonly used in neurology that attracted new attention during the COVID-19 outbreak. This example illustrates some of the ethical challenges associated with the launch of clinical trials to evaluate already approved drugs. In our discussion, we follow the ethics framework for prioritization of COVID-19 clinical trials proposed by Michelle N Meyer and colleagues (2021). We focus on four criteria: social value, scientific validity, feasibility, and consolidation/collaboration. We claim that launching amantadine trials was ethically justified. Although the scientific value was anticipated to be low, unusually, the social value was expected to be high. This was because of significant social interest in the drug. In our view, this strongly supports the need for evidence to justify why the drug should not be prescribed or privately accessed by interested parties. Otherwise, a lack of evidence-based argument could enhance its uncontrolled use. With this paper, we join the discussion on the lessons learned from the pandemic. Our findings will help to improve future efforts to decide on the launch of clinical trials on approved drugs when dealing with the widespread off-label use of the drug.

There is a widespread assumption that facial features could act as a biomarker of human developmental stability and thus provide an important cue to an individual’s physical and mental health status. However, research to date shows mixed support for this assumption. This is the first review that explores the association between various aspects of health and facial features, namely symmetry, averageness, and sexual dimorphism in adults. We searched electronic databases including Web of Science, MEDLINE PubMed, Scopus, and Embase. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines for reporting of our results. Of the 702 screened articles, 21 were eligible for inclusion. Studies presented various relationships between facial features and cardiovascular health; immunocompetence; oxidative stress level; cortisol level; reproductive health; cognitive health, and general physical health. This review results in an inconclusive answer to the question of whether facial features can serve as honest indicators of health. The results warrant caution when utilizing facial features as a biomarker of health status and biological condition of an individual. Protocol: Open Science Framework, https://osf.io/dv9pu/.

Background Oncology research is increasingly adopting new clinical trial models that implement the concept of precision medicine. One of these is the basket clinical trial design. Basket clinical trials allow new treatments to be evaluated across multiple tumor types. Patients recruited to basket clinical trials share certain molecular characteristics of their cancer that are predictive of clinical benefit from the experimental treatment. Objective Our aim was to describe the risks and benefits of basket clinical trials in oncology. Methods Our study was prospectively registered in PROSPERO (CRD42023406401). We systematically searched PubMed, Embase, and ClinicalTrials.gov for reports of basket clinical trials in oncology published between 1 January, 2001, and 14 June, 2023. We measured the risk by treatment-related adverse events (grades 3, 4, and 5), and the benefit by objective response rate. We also extracted and analyzed data on progression-free survival and overall survival. When possible, data were meta-analyzed. Results We included 126 arms of 75 basket clinical trials accounting for 7659 patients. The pooled objective response rate was 18.0% (95% confidence interval [CI] 14.8–21.1). The rate of treatment-related death was 0.7% (95% CI 0.4–1.0), while 30.4% (95% CI 24.2–36.7) of patients experienced grade 3/4 drug-related toxicity. The median progression-free survival was 3.1 months (95% CI 2.6–3.9), and the median overall survival was 8.9 months (95% CI 6.7–10.2). Conclusions Our results provide an empirical basis for communicating about the risks and benefits of basket clinical trials and for refining new models of clinical trials applied in precision medicine.